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Siberian journal of oncology

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Vol 15, No 2 (2016)
View or download the full issue PDF (Russian)
https://doi.org/10.21294/1814-4861-2016-15-2

EPIDEMIOGICAL STUDIES

5-11 909
Abstract

Materials of the research was accepted in the Russian accounting and reporting documents of cial cancer statistics. The article presents the main indicators of medical care for cancer patients in the Amur region, where the 2014 3012 registered new cases of malignant neoplasms, which is 8.9 % more than in the previous year (2013 year – 27.67). Under medical supervision were 15997 patients, i.e. 2 % of the population. Of these, a 45.5 % male and 54.5% female. The maximum number of cases was in the age group 50–69 years. Fewer patients with I–II stages of the process, but it was more of patients with advanced forms of cancer pathology. The number of patients identi ed during preventive examinations amounted to 593 (2013 – 513). Mortality remained at the same level – 120.3 (2013 year – 129.5), whereas the incidence for the last 5 years has increased from 221.7 to in 2010 to 249.9 in 2014 (per 100 000 population). Mortality in the rst year from the time of diagnosis has decreased to 28.4 % (2013 year – 29.4 %). The proportion of patients registered for 5 years or more is 54.5 %. In the cities and districts of the region signi cantly reduced the number of oncologists (2012 year – 22; 2014 year – 13). In 2014 registered 20 cases of malignant neoplasms in children. Data on spatial features of the cancer disease are the basis for the analysis of cancer epidemiology in a speci c region and is aimed primarily at the prevention of this disease. 

CLINICAL STUDIES

12-20 1267
Abstract

Introduction. The prognosis for surgical treatment of locally advanced gastric cancer remains disappointing. Neoadjuvant chemo-radiation therapy is relatively new and the least researched method of treatment, it is attracting more and more attention, mainly abroad in recent years. The aims of neoadjuvant therapy is the earliest start of systemic therapy, damage of the primary tumor and regional metastases, an increase in the percentage of radical operations, improving treatment outcome. Material and methods. The planning study is a multicenter, randomized clinical phase II trial. Patients of the first (experimental) group will be treated as the followes: neoadjuvant chemo-radiotherapy (total tumor dose of 46 Gy in 23 fractions with the concurrent modified CapOX scheme) followed by D2 gastrectomy and adjuvant chemotherapy. Patients of the second (control) group will be treated with D2 gastrectomy and adjuvant chemotherapy. Adjuvant chemotherapy will be carried out under the following schemes (optional for the researchers): CapOX or FOLFOX. Toxicity evaluation of neoadjuvant chemo-radiotherapy and adjuvant chemotherapy will be conducted with NCI CTC Toxicity Scale Version 3.0. The main objectives of the trial are to assess the safety and immediate effectiveness of neoadjuvant chemo-radiotherapy according to the criteria of the frequency and severity of postoperative complications and mortality, and tumor response. We are planning to include 80 patients with morphologically confirmed gastric cancer сT2–4N1–3, сT3–4N0–3; М0. The proposed trial will be carried out in accordance with the principles of the Helsinki Declaration, it has been approved by local ethic committees of the participated institutions. Results. As a result of this multicenter randomized trial it is planned to show the reproducibility of obtained in MRRC and a number of foreign centers results – that is, the safety and high immediate effectiveness of neoadjuvant chemo-radiotherapy in patients with locally advanced gastric cancer. Conclusion. If we reach the goals of the planning trial, the results would allow to reasonably recommend the start of large international phase III trials for the final evaluation of the proposed neoadjuvant treatment as a standard one in patients with locally advanced gastric cancer.

21-28 1374
Abstract

The purpose of the study: to evaluate the efficacy of surgical and combined modality treatment in patients with pelvic chondrosarcoma. Materials and methods. The study included 52 patients with pelvic chondrosarcoma. Forty-two (81 %) patients had well-differentiated and 10 (19 %) patients had poorly differentiated chondrosarcoma. Sixteen (30 %) patients underwent interiliac-abdominal resection of the pelvis and 36 (70 %) patients were treated with organ-preserving surgery. Of the patients treated with organpreserving surgery, 22 (61 %) patients underwent reconstructive surgery. The follow-up period was 45 months (range, 8 –18 months). Results. Positive resection margins were found in 8 (15 %) patients. Postoperative complications were observed in 13 (25 %) patients. The median MSTS score was 92 % (range, 62–100%) for 14 (27 %) patients, who underwent surgery without reconstruction and 67 % (range, 40–95 %) for 22 (61 %) patients, who underwent reconstructive surgery. For 16 (30 %) patients, who underwent interiliacabdominal resection of the pelvis, the median MSTS score was 45 % (range, 25–68 %). Disease progression was observed in 16 (31 %) patients. The overall 5-year survival rate was 75 % and the 5-yaer disease-free survival rate was 60 %. Conclusion. The oncology and functional outcomes are consistent with other recent studies, which indicate that organ-preserving surgery may be an appropriate approach in the treatment of patients with pelvic chondrosarcoma.

29-35 1051
Abstract

The purpose of the study: to evaluate the response to neoadjuvant anthracycline-based chemotherapy depending on the presence of deletions and amplifications of different chromosomal loci and the expression level of topoisomerase 2а in tumor tissue of breast cancer patients. Materials and methods. The study included 46 patients with stage T2–4N0–3M0 breast cancer, who received 2–6 cycles of neoadjuvant chemotherapy with FAC and CAX regimens. Results. The relationship between the expression level of Тор2а>5, deletions of ABCB1, ABCB3, 18р11.21, 11q22.1 loci and amplification of 1q24.1-43 and the response to preoperative treatment was found. Of the 34 patients having at least one of these markers in the tumor tissue, 85.3 % of them demonstrated partial response to neoadjuvant chemotherapy (> 50 % reduction of tumor) and 14.7 % had stable disease and disease progression. No above markers were found in the tumor tissue of 12 patients, who did not respond to preoperative treatment. Conclusion. High levels of Тор2а>5 expression, deletions of ABCB1; ABCB3; 18р11.21; 11q22.1 loci and 1q24.1-43 amplification were shown to be predictive markers of response to neoadjuvant anthracycline-based chemotherapy. The presence of at least one of these markers allowed us to predict response to preoperative treatment in 85 % of cases.

LABORATORY AND EXPERIMENTAL STUDIES

36-41 4541
Abstract

Mutations in KRAS and BRAF genes in 80 colorectal cancer (CRC) samples from Russian patients were tested using two methods: 1) allele-specific real-time PCR (as-rt PCR) and 2) wild-type blocking PCR with Sanger sequencing (WTBS). Material and methods. Sections of fresh frozen or formalin-fixed paraffin embedded tumor tissue from 80 patients were used in the study. Tumor tissue content was determined on H&E stained sections. Samples were first tested by as-rtPCR for common mutations of the KRAS gene (G12C, G12S, G12R, G12V, G12D, G12A, G13D) and mutations BRAFV600E. After that samples were evaluated in PCR with oligonucleotide blocking amplification of wild-type DNA for enrichment with mutant allele followed by Sanger sequencing of the PCR DNA (WTBS method). Results. In 5 (6.3 %) cases samples had low tumor tissue content (<20 %). In reconstruction experiments both methods detected 1–5 % mutant allele. Mutations of KRAS and BRAF genes were found in 37 (46 %) and 3 (3.8 %) of the clinical cases, respectively. Classification in to wild-type and mutant samples by both methods was in agreement in 79 (98.8 %) cases. A single case with rare mutation KRASG13R was detected by WTBS, but was missed by as-rtPCR since this mutation is not included in the test. Of note, KRAS mutations were detected by both tests in two cases with low tumor content. Two cases were found with multiple mutations: one with KRASG12V and G13D, and one with KRASG13D and BRAFV600E. Conclusion. The frequency of mutations in CRC was 46 % for mutations in the KRAS gene, and 3.8 % for the BRAF. We showed 98.8% agreement in KRAS mutation detection by sensitive Sanger sequencing and as-rt PCR. The data on the frequencies of mutations are in agreement with studies in other countries. This in the first study to discover CRC case with multiple mutations KRASG13D and BRAFV600E.

42-47 679
Abstract
The purpose of the study was to evaluate the relationship between the levels of transcription factor, vascular endothelial growth factor (VEGF), serine/threonine-protein kinase (m-TOR), proteasome and calpain activities and the response to everolimus therapy in patients with disseminated renal cell carcinoma. Material and methods. The study included 18 patients with disseminated renal cell carcinoma. The expression of transcription and growth factors was studied using an immune enzymatic assay. Proteasome and calpain activities were evaluated using a fluorometric method. Results. Partial regression and stable disease were observed in 14 (78.8 %) of patients (tumor regression in 22.2 % of patients, stable disease in 56.6 % of patients). Disease progression occurred in 4 (22.2 %) of cases. The objective response to therapy with m-TOR inhibitor was observed in patients with high levels of NF-κB and HIF-1transcription factors, VEGF, VEGFR2 as well as with increased proteasome activity before treatment. Treatment response was also associated with low expression of phospho-m-TOR protein kinase. Conclusion. Additional predictive molecular markers of response to targeted therapy with evorolimus were revealed.
48-55 1030
Abstract
Aberrant methylation of gene promoter regions is the main epigenetic change characterizing colorectal cancer. Methylation levels of 42 CpG-sites of promoter regions of the MGMT, APC and CDH13 genes in colorectal cancer were studied in comparison with methylation levels of the adjacent normal tissue in 25 patients. Pyrosequencing showed an increase in methylation levels of promoter regions of the MGMT, APC and CDH13 genes in tumor samples by 3 to 5 times. These tumor samples were screened for activating SNP-mutations in the KRAS (40 %), NRAS (0 %) and BRAF (0 %) oncogenes. SNP-mutations in the KRAS gene were accompanied by hypermethylation of one or more promoters of the studied genes. Association of this epigenetic index with tumor metastasis was proved. The data on an increase in methylation of the promoter regions of oncosupressor genes can be used as sensitive prognostic markers of progression and metastasis of colorectal cancer.

ONCOLOGY PRACTICE

56-62 929
Abstract
To reconstruct defects of the oral cavity in patients with oral cancer, various displaced and free flaps are used. The paper presents the treatment outcomes of patients who underwent reconstruction of oral defects using the submental flap.
63-68 2040
Abstract
The purpose of the study was to evaluate the role of surgery in the treatment of patients with small cell lung carcinoma in order to improve treatment outcomes. Material and methods. Long-term surgical treatment outcomes in 41 patients were analyzed. Twenty six patients underwent lobectomy and 15 patients underwent pneumonectomy. Results. The 5-year survival rates were 66, 29 and 21 % in patients with stage I, II and III small cell lung carcinoma, respectively. The 5-year survival rate following systematic lymph node dissection was significantly higher than following systematic biopsy (61 % versus 24 %). Conclusion. Surgical treatment including lobectomy or pneumonectomy with systematic lymph node dissection followed by adjuvant chemotherapy is recommended for patients with stage I and II small cell lung carcinoma.

REVIEWS

69-75 1267
Abstract
The review presents the diagnostic value of magnetic resonance imaging (MRI) in the diagnosis of soft tissue sarcoma in the pre-hospital period and during combined modality treatment was studied. Findings of using MRI in the assessment of local tumor extent and diffusion-weighted MRI and dynamic contrast-enhanced MRI in the estimation of the effectiveness of preoperative treatment were presented.
76-89 1332
Abstract
In this review, the latest data on factors influencing efficiency of the treatment of locally advanced inoperable stage III non-small cell lung cancer (NSCLC) are analyzed. Concomitant chemoradiotherapy (CRT) is a current standard of treatment with the 5-year overall survival rate of 20–30 % and median survival time of 17–28 months. However, only a small proportion of patients (13–35 % by the data from population-based studies) can receive CRT. Radiotherapy is currently progressing towards new approaches, including IMRT and IGRT, showing promising results, however, these approaches are still experimental. Accelerated repopulation of clonogens is biological factor necessitating intensification of both RT and chemotherapy. For RT, accelerated hyperfractionation is an optimal way for that. There is some data evidencing negative role of delays in the radiation treatment to overall efficacy and even survival. Therefore, the optimal approach to the treatment of Stage III NSCLC seems to be early beginning of RT and short overall time for both RT and chemotherapy.
90-100 1275
Abstract

The literature review presents the modern methods of treatment of inoperable recurrent squamous cell cancer of the larynx. The application of radiation and chemotherapy.

101-106 1274
Abstract
This review presents information about one of the promising areas of targeted therapy in modern oncology, which is called radioimmunotherapy. Particular attention is paid to the possibility of clinical application of this type of systemic treatment for patients with both hematologic malignancies and solid tumors.
107-112 1955
Abstract

Colorectal anastomosis failure is one of the serious complications following abdominoperineal resection of the rectum, accounting for approximately 40 % of cases. Mortality rate in patients with colorectal anastomosis was reported to be 39 % and above 90 % in cases with anastomosis located in the abdomen. The literature analysis showed the importance of the problem of colorectal anastomosis failure, thus dictating the necessity of searching for the new methods of prevention and treatment for this serious complication. The aim of the study was to analyze the literature on the risk factors for colorectal anastomosis. The main factor influencing anastomotic leakage is the height of the anastomosis above the anal verge. The authors’ data were often contradictory.

CASE REPORTS

113-118 860
Abstract
The article describes the historical background of the first described case of detection of solitary fibrous tumor of the pleura, reflects the principles of clinical, instrumental and morphological diagnosis. Presented clinical case of successful surgical treatment of recurrent solitary fibrous tumor of the pleura after previously performed lung resection for water intended metastatic breast cancer.

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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)